Transmission Blocking Activity of Low Dose Tafenoquine in Healthy Volunteers Experimentally Infected with Plasmodium Falciparum

Background Blocking the transmission of parasites from humans to mosquitoes is a key component of malaria control. Tafenoquine exhibits activity against all stages of the malaria parasite and may have utility as a transmission blocking agent. We aimed to characterize the transmission blocking activity of low dose tafenoquine.Methods Healthy adults were inoculated with P. falciparum 3D7-infected erythrocytes on day 0. Piperaquine was administered on days 9 and 11 to clear asexual parasitemia while allowing gametocyte development. A single 50 mg oral dose of tafenoquine was administered on day 25. Transmission was determined by enriched membrane feeding assays pre-dose and at 1, 4 and 7 days post-dose. Artemether-lumefantrine was administered following the final assay. Outcomes were the reduction in mosquito infection and gametocytemia post-tafenoquine, and safety parameters.Results Six participants were enrolled, and all were infective to mosquitoes pre-tafenoquine, with a median 86% (range: 22–98) of mosquitoes positive for oocysts and 57% (range: 4–92) positive for sporozoites. By day 4 post-tafenoquine, the oocyst and sporozoite positivity rate had reduced by a median 35% (IQR: 16–46) and 52% (IQR: 40–62), respectively, and by day 7, 81% (IQR 36–92) and 77% (IQR 52–98), respectively. The decline in gametocyte density post-tafenoquine was not significant. No significant participant safety concerns were identified.Conclusion Low dose tafenoquine reduces P. falciparum transmission to mosquitoes, with a delay in effect.Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12620000995976).Funding QIMR Berghofer Medical Research Institute.### Competing Interest StatementThe authors have declared no competing interest.### Clinical TrialACTRN12620000995976### Funding StatementThis study was funded by the QIMR Berghofer Medical Research Institute (Brisbane, Australia).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by the QIMR Berghofer Medical Research Institute Human Research Ethics Committee (reference number P3646) with mutual recognition of the ethical review of the QIMR Berghofer HREC P3646 by the Departments of Defence and Veterans Affairs Human Research Ethics Committee (DDVA HREC 194-19).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors.